Inhibitory effects of interferon-g on activation of rat pancreatic stellate cells are mediated by STAT1 and involve down-regulation of CTGF expression

• Published in: Cellular signalling Vol. 19; no. 4; pp. 782 - 790
• Main Authors: Fitzner, Brit, Brock, Peter, Nechutova, Hana, Glass, Anne, Karopka, Thomas, Koczan, Dirk, Thiesen, Hans-Jurgen, Sparmann, Gisela, Emmrich, Jorg, Liebe, Stefan, Jaster, Robert
• Format: Journal Article
• Language: English
• Published: 01.04.2007
• ISSN: 0898-6568
• DOI: 10.1016/j.cellsig.2006.10.002

Pancreatic stellate cells (PSCs) are the main source of extracellular matrix proteins in pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Interferon-g (IFN-g) is an antifibrotic cytokine, but how precisely it exerts its effects on PSCs is largely unknown. Here, we have focussed on the role of STAT1 as well as target genes of IFN-g signalling. Our data indicate that IFN-g regulates the expression of two autocrine mediators of PSC activation, connective tissue growth factor and endothelin-1, in a transforming growth factor-b1-antagonistic manner. STAT1 overexpression under the control of a tetracycline-dependent promoter revealed a close correlation between STAT1 expression and activation, the biological effects of IFN-g (growth inhibition, induction of apoptosis), and target gene expression. Our data further support the hypothesis that IFN-g interferes with stellate cell activation in the pancreas and suggest activated STAT1 as an inductor of a quiescent PSC phenotype.